Biomaterial

Adiponectin, leptin and ghrelin


Data files
LASAG879

Contact: Natasja van Schoor

Background
Adiponectin circulates in the blood in multiple isoforms. High-molecular-weight adiponectin has a predominant role in many pathophysiological mechanisms amongst which the development of diabetes mellitus type 2 and cardiac pathology. As HMW adiponectin has both pro- and anti-inflammatory effects, it is dependent on the phase of the underlying disease what the exact role of HMW adiponectin is1.

Leptin and ghrelin function as anorexigenic and orexigenic hormones respectively and as such regulate energy homeostasis. Leptin also has comprehensive mechanisms of action in the central nervous system and is therefore associated with the development of Alzheimer’s disease and depression2. Systemic effects of ghrelin include growth hormone release, stimulation of gastro-intestinal motility and metabolic effects such as inhibition of insulin secretion and regulation of cholesterol profile3.

Adiponectin, leptin and ghrelin have previously been associated with the development of dementia, although the associations per hormone differ2,5,6.

Measurement in LASA
At cycle G (2008 / 2009) blood samples were drawn after an overnight fast. Samples were stored at -70˚C until analysis in 2016. All analyses where performed at the Endocrine Laboratory, Department of Clinical Chemistry of the Amsterdam University Medical Center, location VUmc.

High-molecular-weight adiponectin (HMW adiponectin) was measured using a fully-automated immunoanalyzer (Lumipulse, Fujirebo, Japan, IH7 monoclonal antibodies) with an intra-assay variation of 2.3%4.

Ghrelin was determined using a total ghrelin RIA (Millipore). The lower limit of quantitation is 240 pg/mL. The inter-assay variation of this assay is <7% for the whole concentration range.

Leptin was measured using a radioimmunoassay (RIA) (Millipore, St Charles, Missouri, USA). The lower limit of quantitation is 0.5g/L. The inter-assay variation of this assay is <6% for the whole concentration range.

Availability of data

At cycle G 935 out of 1494 participants had routine blood samples done. In 898 cases there was surplus blood after routine sampling and HMW adiponectin, leptin and ghrelin could be determined. Due to technical issues a few samples did not return valid results, so the final data set included 896 cases for HMW adiponectin and leptin and 897 cases for ghrelin, see Table 1 below.

Table 1. Response combined first (n=761) and second (n=733) cohort

Cycle

Total medical interview

Number
of blood samples

Number
of surplus blood samples

Number of valid cases

Response (%)

G

1494

935

898

896

57,6


Previous use in LASA
In LASA, we have examined the association between aforesaid hormones and age-related cognitive decline at baseline (cycle G) and after three years of follow-up (cycle H) in a sex-stratified analysis. We found that at baseline HMW adiponectin is associated with better baseline cognitive function in women only, however after three years of follow-up there was an inverse association between HMW adiponectin and age-related cognitive decline, again in women only. We found no significant associations between HMW adiponectin and age-related cognitive decline in men or leptin and ghrelin and age-related cognitive decline in either men or women.

References

  1. van Andel M, Heijboer AC, Drent ML. Adiponectin and Its Isoforms in Pathophysiology. Advances in Clinical Chemistry. 2018;85.
  2. Kiliaan AJ, Arnoldussen IA, Gustafson DR. Adipokines: a link between obesity and dementia? Lancet Neurol. 2014;13(9):913-923.
  3. Muller TD, Nogueiras R, Andermann ML, et al. Ghrelin. Mol Metab. 2015;4(6):437-460.
  4. van Andel M, Drent ML, van Herwaarden AE, Ackermans MT, Heijboer AC. A method comparison of total and HMW adiponectin: HMW/total adiponectin ratio varies versus total adiponectin, independent of clinical condition. Clin Chim Acta. 2017;465:30-33.
  5. Van Himbergen TM, Beiser AS, Ai M, et al. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease: Results from the Framingham Heart Study. Archives of Neurology. 2012;69(5):594-600.
  6. Kang S, Moon NR, Kim DS, Kim SH, Park S. Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with beta-amyloid. Peptides. 2015;71:84-93.